Department of Internal Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Oncology Center, King Saud University Medical City, Riyadh, Saudi Arabia.
PLoS One. 2024 Jun 7;19(6):e0304241. doi: 10.1371/journal.pone.0304241. eCollection 2024.
Evidence supports the benefits of hydroxyurea (HU) in adults with sickle cell disease (SCD), but reservations remain due to long-term concerns of fertility. Retrospective analysis of clinical records of SCD patients (haemoglobin SS genotype) have identified gender-related differences in disease progression. This could inform risk stratification during SCD at diagnosis with the possibility to guide therapeutic decisions.
This systemic review and meta-analysis evaluated fertility parameters in both children (aged ≥ 6 years) and adults with SCD receiving HU therapy. Studies were sourced from PubMed and EMBASE from inception to July 2023. A total of 160 potentially relevant articles were identified.
Four studies were included that evaluated the effects of HU on sperm parameters in males. A further 4 studies assessed anti-mullerian hormone (AMH) levels and ovarian reserves in females. Differences from baseline values were used to identify compromised fertility. Amongst males, HU treatment negatively impacted the concentration of spermatozoa (MD = -15.48 million/mL; 95% CI: [-20.69, -10.26]; p< 0.001), which continued following treatment cessation (MD = -20.09 million/mL; 95% CI: [-38.78, -1.40]; P = 0.04). HU treatment also led to lower total sperm counts (MD = -105.87 million; 95% CI: [-140.61, -71.13]; P< 0.001) which persisted after treatment (MD = -53.05 million; 95% CI: [-104.96, -1.14]; P = 0.05). Sperm volume, initial forward motility and morphology were unaffected by HU treatment. In females, HU treatment decreased the mean AMH levels 1.83 (95% CI [1.42, 2.56]. A total of 18.2.% patients treated with HU showed reduced ovarian reserves.
INTERPRETATION & CONCLUSIONS: This systemic review and meta-analysis suggest that the use of HU for SCD impacts seminal fluid parameters in males and can diminish AMH levels and ovarian reserves in females.
有证据表明羟基脲（HU）可使镰状细胞病（SCD）患者受益，但由于长期关注生育问题，该药物的应用仍存在一些顾虑。对 SCD 患者（血红蛋白 SS 基因型）的临床记录进行回顾性分析发现，疾病进展存在性别差异。这可以为 SCD 诊断时的风险分层提供信息，并有可能指导治疗决策。
本系统评价和荟萃分析评估了接受 HU 治疗的 SCD 儿童（年龄≥6 岁）和成人的生育参数。研究资料来源于从建库至 2023 年 7 月的 PubMed 和 EMBASE。共确定了 160 篇潜在相关文章。
纳入了 4 项研究，评估 HU 对男性精子参数的影响。另外 4 项研究评估了女性抗苗勒管激素（AMH）水平和卵巢储备情况。使用基线值差异来确定生育能力受损情况。在男性中，HU 治疗使精子浓度降低（MD=-15.48 百万/ml；95%CI：[-20.69，-10.26]；p<0.001），停药后仍持续降低（MD=-20.09 百万/ml；95%CI：[-38.78，-1.40]；P=0.04）。HU 治疗还导致总精子计数降低（MD=-105.87 百万；95%CI：[-140.61，-71.13]；P<0.001），停药后仍持续降低（MD=-53.05 百万；95%CI：[-104.96，-1.14]；P=0.05）。HU 治疗对精子体积、初始前向运动和形态无影响。在女性中，HU 治疗使 AMH 水平平均降低 1.83（95%CI [1.42, 2.56]）。共有 18.2%接受 HU 治疗的患者出现卵巢储备减少。
本系统评价和荟萃分析表明，SCD 患者使用 HU 会影响男性的精液参数，并可能降低女性的 AMH 水平和卵巢储备。
